Screening the absorbed active components of Danggui Sini Decoction in the treatment of diabetic peripheral neuropathy by network pharmacology combined with molecular docking and dynamics simulation

Diabetic peripheral neuropathy (DPN) is a prevalent and detrimental condition that can be debilitating and even fatal if not treated; however, there remains a dearth of efficacious pharmaceutical interventions for DPN. The Danggui Sini Decoction (DSD), a renowned traditional Chinese medicine prescription, has been utilized in the clinic for the treatment of DPN because of its efficacy in addressing yang deficiency and cold coagulation. However, the active components and underlying mechanisms of DSD remain unclear. In this study, we devised a conventional approach to screen the absorbed active ingredients in DSD, employing LC-MS to identify the principal active compounds of DSD in the blood of rats and then validating these components using network pharmacology for target prediction and molecular dynamics simulations for further validation. We identified 17 potentially active components in the serum and 47 main targets that might be relevant for treating DPN with DSD. These targets were associated with pathways including neuroactive ligand-receptor interaction, HIF-1, and AGE-RAGE signaling pathways, all of which are implicated in diabetic complications. Through molecular docking, we found that glycyrrhetinic acid and betulonic acid-two active components identified by LC-MS in the DSD-containing serum of rats-exhibited strong binding activities with AKT1 and STAT3. Furthermore, molecular dynamics simulations of the docking results indicated that the AKT1-glycyrrhetinic acid and AKT1-betulonic acid complexes were highly stable throughout the kinetic simulations. These findings suggest that the molecular mechanism underlying DSD treatment of DPN may involve the activation of AKT1 by glycyrrhetinic acid and betulonic acid.